Ixekizumab effective for difficult-to-treat psoriatic arthritis

The monoclonal antibody ixekizumab improved the signs and symptoms of psoriatic arthritis (PsA) in PsA patients with inadequate response to one or two tumour necrosis factor inhibitors (TNFis), suggests results from a post hoc subanalysis of the SPIRIT-P2 trial.

“Patients with PsA who have had inadequate response to TNFis present specific challenges to clinicians and have not been studied extensively (particularly two TNFis) in dedicated clinical studies … Patients who switch to a second TNFi have worse responses than those who do not switch, and drug survival for a second-line TNFi is lower than for first-line TNFis,” said the researchers.

“Treatments with different mechanisms of action may be an option for patients with PsA who have failed one or more TNFis … Previously, we showed that ixekizumab provides comparable efficacy between patients who have inadequate response to one [and two TNFis], as measured by ACR20*,” they added. [Lancet 2017;389:2317-2327]

“[W]e further investigated the effect of ixekizumab in a subgroup of patients who had inadequate response to one and two TNFis, including more relevant clinical endpoints such as the simultaneous achievement of ACR50* and PASI 100**, ACR50, HAQ-DI*** ≥0.35 improvement, EULAR*** good response (absolute ≤3.2 and improvement in DAS28-CRP*** >1.2), DAPSA*** ≤14, and MDA***,” they continued.

A total of 332 participants were randomized 1:1:1 to receive SC ixekizumab 80 mg Q4W (the approved dosing regimen for active PsA) or Q2W after a 160-mg starting dose, or placebo, through week 24. Of these, 204 and 128 had inadequate response to one TNFi (one-TNFi-IR) and two TNFis^# (two-TNFi-IR), respectively. At week 16, inadequate responders^## were required to add/alter concomitant medications (csDMARD^###, methotrexate). By week 24, placebo recipients were rerandomized to either ixekizumab Q4W or Q2W for the rest of the study, while those on ixekizumab remained on their original dose. [Rheumatology 2021;60:4367-4372]

Regardless of previous TNFi experience, more ixekizumab vs placebo recipients simultaneously achieved ACR50 and PASI 100 (31 percent [one-TNFi-IR] and 29 percent [two-TNFi-IR] vs 0 percent), ACR50 (63 percent and 71 percent vs 10 percent), HAQ-DI ≥0.35 improvement (79 percent and 93 percent vs 33 percent), and EULAR good response (83 percent and 76 percent vs 15 percent) at week 24.

More patients on ixekizumab were also able to achieve the more stringent outcomes of MDA (52 percent [one-TNFi-IR] and 48 percent [two-TNFi-IR] vs 7 percent) and DAPSA ≤14 (79 percent and 60 percent vs 21 percent) as opposed to those on placebo.

By week 52, there were similar proportions of ixekizumab Q4W recipients who simultaneously achieved ACR50 and PASI 100, both in the one- (25 percent) and two-TNFi-IR subgroups (22 percent). The proportions of participants achieving ACR50 were also similar between the two subgroups (41 percent and 44 percent, respectively).

However, the study was not designed to evaluate differences between the TNFi-IR subgroups. The lack of a placebo arm after week 24 may have also limited the findings. “[Moreover,] it is difficult to assess outcome measures that further reduce the population size (eg, plaque psoriasis, enthesitis, or dactylitis). Furthermore … it is unclear whether patients have primary or secondary TNFi failures, which may have provided more insights around the results,” the researchers noted.

“[Nonetheless, in this subanalysis,] patients on ixekizumab Q4W and Q2W achieved superior outcomes compared with those on placebo at week 24, and the effects [on all outcomes analysed] were sustained to week 52, regardless of prior inadequate response to one or two TNFis,” said the researchers.

“Therefore, ixekizumab may provide clinicians with an effective treatment option for patients with PsA who have failed one or two TNFis … These data are increasingly important because other mode-of-action therapies are now available,” they concluded.